The Pima Indian population of Arizona has one of the highest reported prevalence rates of obesity in the world. To determine whether a "thrifty" gene is the genetic defect predisposing the Pima Indians to obesity, we have investigated different components of the daily energy expenditure in both Pima Indians and Caucasians. Basal metabolic rate have been measured by an open circuit hood system indirect calorimeter, whereas the other components of 24-hour energy expenditure, i.e. the cost of physical activity and the thermic effect of meals, have been measured using a respiratory chamber. The cross-sectional and longitudinal results to date have shown that: 1) the rate of resting or 24-hour energy metabolism is a familial trait independent of individual differences in body size, age, and sex, 2) reduced resting or 24-hour energy expenditure rates are associated with an increased risk of weight gain, 3) the thermic effect of food is independent of the degree of obesity, 4) part of the differences in energy expenditure observed between people can be attributed to differences in the level of sympathetic nervous system activity, 5) spontaneous physical activity or "fidgeting" represents 100-800 kcal/day of the total energy expenditure, and may therefore predispose to obesity in the least active subjects. We are continuing to use the respiratory chamber to investigate the short-term energy metabolism response to over- and underfeeding in adults as well as the response to mild overfeeding in children from families with or without a history of obesity.